1. Field of the Invention
The present invention is broadly concerned with improved, commercially feasible methods for the simultaneous precipitation of material (particularly medicaments) within a plurality of containers using near-supercritical or supercritical antisolvent gas such as carbon dioxide.
2. Description of the Prior Art
U.S. Pat. No. 5,833,891 describes greatly improved methods for the precipitation of particles such as medicaments using near-supercritical or supercritical antisolvents. These methods generally involve spray techniques wherein the interphase mass transfer rate is maximized between small droplets of the dispersion and antisolvent gas so as to generate very small precipitated particles. This patent also teaches that medicaments can be prepared and administered to a patient without the necessity of transferring the medicament between containers. That is, a dispersion/antisolvent precipitation is carried out in a final use container which is consequently sealed to permit later withdraw of medicament doses from the use container. This technique generally involves lyophobic precipitation of medicaments on a batch or semi-batch basis. However, the methods taught for this process involve use of long glass tubes sealed at one end with glass frits. Such fritted tubes are not at all suitable for commercial production of medicaments, and thus the specific single vial techniques described in the '891 patent are of limited commercial potential.
U.S. Pat. No. 6,620,351 is also concerned with formation of nanoparticles using supercritical fluid antisolvents. In this case, a dispersion containing a desired material to be precipitated is applied on or very close to an ultrasonic vibrating surface to generate small droplets. An antisolvent at near-supercritical or supercritical conditions is also applied adjacent the vibrating surface in order to precipitate the desired particles. Here again, the requirement for direct or near contact between the ultrasonic vibrating surface and the material-containing dispersion means that the process cannot be effectively used on a commercial scale. This is because containers would need to be individually treated, or an individual vibratory surface would need to be provided for each container. In either case, the cost and complexity of such a system would materially detract from the usefulness of the process.